The principal aim of this study is to assess the longitudinal development of specific neuroanatomy in individuals with fragile X syndrome. Over the past year, funds from the PCRU have covered the cost of MRIs for seven new research subjects (1-fragile X premutation, 3-fragile X full mutations, and 3-controls). Since the approval date of 7/11/95, a total of nine subjects (2additional with the full mutation) have participated in our PCRU funded research. Of the nine subjects scanned thus far, three have the fragile X full mutation and have been scanned at an earlier age. These three subjects are the most interesting to consider at this preliminary stage of the data collection because they have the most severe form of the fragile X mutation. In order to assess the effect of age on cerebellar vermis, data from the three PCRU subjects were combined with that from six other fragile X full mutation subjects who have previously received more than one MRI scan. We have observed that the posterior cerebellar vermis is smaller in subjects with fragile X syndrome, there, we used these first nine subjects to assess whether or not this structure's size appears decreases with time. Repeated measures ANOVA indicate that with subject posterior vermis area does not significantly change with time (n=9, ICC=.81,P=.16). Graphical inspection of the posterior vermis/intracranial ratio in nine subjects assessed to date is consistent with the results from the ANOVA as it does not indicate any clear pattern of longitudinal decline or change. We are currently in the process of analyzing other structures of the brain in oder to assess for a possible age effect. These structures will include volumetric assessment of the amygdala, hippocampus, caudate nucleus and four lobes of the cortex. These volumetric analyses require a specific MRI scan protocol known as an SPGR. All the PCRU subjects mentioned above have received the necessary SPGR scan, however, only 3 of the fragile X subjects have received such scans in the past because this MRI protocol is relatively new compared to the sagittal-T1 scan used to measure the cerebellar vermis. As a result, no longitudinal volumetric analysis has been conducted. By this time next year we expect to have at least 10 fragile X subjects with multiple SPGR scans so that we can quantitatively assess the longitudinal of several three dimensional structures of the brain.